Genetic Variant CEP72:p.Asp135Asp (chr5-624472-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018140.4(CEP72):c.405C>T(p.Asp135Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,613,180 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 30 hom. )

Consequence

CEP72
NM_018140.4 splice_region, synonymous

Scores

Splicing: ADA: 0.000009227

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.660

Variant links:

Genes affected

CEP72 (HGNC:25547): (centrosomal protein 72) The product of this gene is a member of the leucine-rich-repeat (LRR) superfamily of proteins. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. [provided by RefSeq, Jul 2008]

CEP72 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 5-624472-C-T is Benign according to our data. Variant chr5-624472-C-T is described in ClinVar as [Benign]. Clinvar id is 775221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.66 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00542 (826/152334) while in subpopulation AMR AF= 0.0171 (262/15306). AF 95% confidence interval is 0.0154. There are 9 homozygotes in gnomad4. There are 398 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP72	NM_018140.4 link	c.405C>T	p.Asp135Asp	splice_region_variant, synonymous_variant	Exon 4 of 12	ENST00000264935.6	NP_060610.2	Q9P209-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP72	ENST00000264935.6 link	c.405C>T	p.Asp135Asp	splice_region_variant, synonymous_variant	Exon 4 of 12	1	NM_018140.4	ENSP00000264935.5		Q9P209-1

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00220

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00430

AC:

1082

AN:

251406

Hom.:

AF XY:

0.00417

AC XY:

566

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.00782

GnomAD4 exome

AF:

0.00274

AC:

4009

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

2014

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00688

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.00542

AC:

826

AN:

152334

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

398

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00770

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00220

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00727

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 06, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.5

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000092

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over